title: Long-term risk of clinical progression after biochemical recurrence following radical prostatectomy: the impact of time from surgery to recurrence.
abstract: BACKGROUND
  The natural history of biochemical recurrence (BCR) after radical retropubic prostatectomy (RRP) is variable and does not always translate into systemic progression or prostate cancer (PCa) death.
  
  
  OBJECTIVE
  To evaluate long-term clinical outcomes of patients with BCR and to determine predictors of disease progression and mortality in these men.
  
  
  METHODS
  We reviewed our institutional registry of 14 632 patients who underwent RRP between 1990 and 2006 to identify 2426 men with BCR (prostate-specific antigen [PSA] levels ≥ 0.4 ng/ml) who did not receive neoadjuvant or adjuvant therapy. Median follow-up was 11.5 yr after RRP and 6.6 yr after BCR.
  
  
  METHODS
  RRP.
  
  
  METHODS
  Patients were grouped into quartiles according to time from RRP to BCR. Survival after BCR was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazard regression models were used to analyze clinicopathologic variables associated with systemic progression and death from PCa.
  
  
  CONCLUSIONS
  Median systemic progression-free survival (PFS) and cancer-specific survival (CSS) had not been reached after 15 yr of follow-up after BCR. Cancer-specific mortality 10 yr after BCR was 9.9%, 9.3%, 7.8%, and 4.7% for patients who experienced BCR <1.2 yr, 1.2-3.1 yr, 3.1-5.9 yr, and >5.9 yr after RRP, respectively (p=0.10). On multivariate analysis, time from RRP to BCR was not significantly associated with the risk of systemic progression (p=0.50) or cancer-specific mortality (p=0.81). Older patient age, increased pathologic Gleason score, advanced tumor stage, and rapid PSA doubling time (DT) predicted systemic progression and death from PCa. Limitations included retrospective design, varied utilization of salvage therapies, and the inclusion of few patients with positive lymph nodes.
  
  
  CONCLUSIONS
  Only a minority of men experience systemic progression and death from PCa following BCR. The decision to institute secondary therapies must balance the risk of disease progression with the cost and morbidity of treatment, independent of time from RRP to BCR.
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA. boorjian.stephen@mayo.edu
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.forename: R Houston
authors.initials: RH
authors.lastname: Thompson
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Tollefson
authors.forename: Laureano J
authors.initials: LJ
authors.lastname: Rangel
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bergstralh
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blute
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
mesh_terms: D000367:Age Factors; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008910:Minnesota; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D018579:Patient Selection; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000009:adverse effects / Q000401:mortality; D011471:Prostatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D017430:Prostate-Specific Antigen